ID   BX4_LOXGA               Reviewed;          35 AA.
AC   P0C2K6;
DT   06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   16-OCT-2019, entry version 31.
DE   RecName: Full=Dermonecrotic toxin LgSicTox-beta-LOXN4;
DE            EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE   AltName: Full=Phospholipase D;
DE            Short=PLD;
DE   AltName: Full=Sphingomyelin phosphodiesterase D;
DE            Short=SMD;
DE            Short=SMase D;
DE            Short=Sphingomyelinase D;
DE   Flags: Fragments;
OS   Loxosceles gaucho (Spider).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Araneae; Araneomorphae; Haplogynae; Sicariidae; Loxosceles.
OX   NCBI_TaxID=58216;
RN   [1]
RP   PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=15852345; DOI=10.1002/pmic.200401096;
RA   Machado L.F., Laugesen S., Botelho E.D., Ricart C.A.O., Fontes W.,
RA   Barbaro K.C., Roepstorff P., Sousa M.V.;
RT   "Proteome analysis of brown spider venom: identification of
RT   loxnecrogin isoforms in Loxosceles gaucho venom.";
RL   Proteomics 5:2167-2176(2005).
CC   -!- FUNCTION: Dermonecrotic toxins cleave the phosphodiester linkage
CC       between the phosphate and headgroup of certain phospholipids
CC       (sphingolipid and lysolipid substrates), forming an alcohol (often
CC       choline) and a cyclic phosphate (By similarity). This toxin acts
CC       on sphingomyelin (SM) (By similarity). It may also act on ceramide
CC       phosphoethanolamine (CPE), lysophosphatidylcholine (LPC) and
CC       lysophosphatidylethanolamine (LPE), but not on
CC       lysophosphatidylserine (LPS), and lysophosphatidylglycerol (LPG)
CC       (By similarity). It acts by transphosphatidylation, releasing
CC       exclusively cyclic phosphate products as second products (By
CC       similarity). Induces dermonecrosis, hemolysis, increased vascular
CC       permeability, edema, inflammatory response, and platelet
CC       aggregation (By similarity). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC       ECO:0000250|UniProtKB:P0CE80}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-(acyl)-sphingosylphosphocholine = an N-(acyl)-
CC         sphingosyl-1,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60652,
CC         ChEBI:CHEBI:15354, ChEBI:CHEBI:64583, ChEBI:CHEBI:143892;
CC         Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-(acyl)-sphingosylphosphoethanolamine = an N-(acyl)-
CC         sphingosyl-1,3-cyclic phosphate + ethanolamine;
CC         Xref=Rhea:RHEA:60648, ChEBI:CHEBI:57603, ChEBI:CHEBI:143891,
CC         ChEBI:CHEBI:143892; Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1-acyl-sn-glycero-3-phosphocholine = a 1-acyl-sn-
CC         glycero-2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60700,
CC         ChEBI:CHEBI:15354, ChEBI:CHEBI:58168, ChEBI:CHEBI:143947;
CC         Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1-acyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-sn-
CC         glycero-2,3-cyclic phosphate + ethanolamine;
CC         Xref=Rhea:RHEA:60704, ChEBI:CHEBI:57603, ChEBI:CHEBI:64381,
CC         ChEBI:CHEBI:143947; Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q8I914};
CC       Note=Binds 1 Mg(2+) ion per subunit.
CC       {ECO:0000250|UniProtKB:Q8I914};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15852345}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:15852345}.
CC   -!- PTM: Contains 2 disulfide bonds. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class
CC       II subfamily. {ECO:0000305}.
CC   -!- CAUTION: The most common activity assay for dermonecrotic toxins
CC       detects enzymatic activity by monitoring choline release from
CC       substrate. Liberation of choline from sphingomyelin (SM) or
CC       lysophosphatidylcholine (LPC) is commonly assumed to result from
CC       substrate hydrolysis, giving either ceramide-1-phosphate (C1P) or
CC       lysophosphatidic acid (LPA), respectively, as a second product.
CC       However, two studies from Lajoie and colleagues (2013 and 2015)
CC       report the observation of exclusive formation of cyclic phosphate
CC       products as second products, resulting from intramolecular
CC       transphosphatidylation. Cyclic phosphates have vastly different
CC       biological properties from their monoester counterparts, and they
CC       may be relevant to the pathology of brown spider envenomation.
CC       {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC       ECO:0000250|UniProtKB:A0A0D4WV12, ECO:0000250|UniProtKB:Q4ZFU2}.
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DR   ArachnoServer; AS000153; Sphingomyelinase D (LOXN4) (N-terminal fragment).
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0044179; P:hemolysis in other organism; IEA:UniProtKB-KW.
DR   GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Cytolysis; Dermonecrotic toxin; Direct protein sequencing;
KW   Disulfide bond; Hemolysis; Lipid degradation; Lipid metabolism; Lyase;
KW   Magnesium; Metal-binding; Secreted; Toxin.
FT   CHAIN         1    >35       Dermonecrotic toxin LgSicTox-beta-LOXN4.
FT                                /FTId=PRO_0000279563.
FT   METAL        20     20       Magnesium. {ECO:0000250}.
FT   NON_CONS      8      9       {ECO:0000305}.
FT   NON_CONS     22     23       {ECO:0000305}.
FT   NON_TER      35     35
SQ   SEQUENCE   35 AA;  4021 MW;  22042E1EE589DA0B CRC64;
     ADSRKPDDRY DMSGNDALGD VKLATYEDNP WETFK
//
ID   CCY1B_CHRCN             Reviewed;          34 AA.
AC   P0DP94;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2017, sequence version 1.
DT   05-DEC-2018, entry version 6.
DE   RecName: Full=Mu-theraphotoxin-CCy1b {ECO:0000303|PubMed:25754331};
DE            Short=Mu-TRTX-CCy1b {ECO:0000303|PubMed:25754331};
OS   Chromatopelma cyaneopubescens (Greenbottle blue tarantula) (Eurypelma
OS   cyaneopubescens).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Araneae; Mygalomorphae; Theraphosidae; Chromatopelma.
OX   NCBI_TaxID=1795674;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Venom;
RX   PubMed=25754331; DOI=10.1111/bph.13081;
RA   Klint J.K., Smith J.J., Vetter I., Rupasinghe D.B., Er S.Y., Senff S.,
RA   Herzig V., Mobli M., Lewis R.J., Bosmans F., King G.F.;
RT   "Seven novel modulators of the analgesic target NaV 1.7 uncovered
RT   using a high-throughput venom-based discovery approach.";
RL   Br. J. Pharmacol. 172:2445-2458(2015).
CC   -!- FUNCTION: Voltage-gated sodium channel Nav1.7/SCN9A inhibitor.
CC       {ECO:0000269|PubMed:25754331}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25754331}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:25754331}.
CC   -!- MASS SPECTROMETRY: Mass=4115.6; Method=MALDI; Range=1-34;
CC       Note=Monoisotopic mass.; Evidence={ECO:0000269|PubMed:25754331};
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 22 (Htx-
CC       4) subfamily. {ECO:0000305}.
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DR   SMR; P0DP94; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR011696; Huwentoxin-1.
DR   InterPro; IPR013140; Huwentoxin_CS1.
DR   Pfam; PF07740; Toxin_12; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN         1     34       Mu-theraphotoxin-CCy1b.
FT                                {ECO:0000269|PubMed:25754331}.
FT                                /FTId=PRO_0000441852.
FT   DISULFID      3     18       {ECO:0000250|UniProtKB:D2Y1X7}.
FT   DISULFID     10     23       {ECO:0000250|UniProtKB:D2Y1X7}.
FT   DISULFID     17     30       {ECO:0000250|UniProtKB:D2Y1X7}.
SQ   SEQUENCE   34 AA;  4125 MW;  8D9333EF292632FA CRC64;
     DDCLGFFKSC NPDNDKCCEN YKCNRRDKWC KYVL
//
ID   CT1B_CORTR              Reviewed;          82 AA.
AC   P0DL78;
DT   22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2017, sequence version 1.
DT   08-MAY-2019, entry version 4.
DE   RecName: Full=U1-theraphotoxin-Ct1b {ECO:0000303|PubMed:27793656};
DE            Short=U1-TRTX-Ct1b {ECO:0000303|PubMed:27793656};
DE   Flags: Precursor;
OS   Coremiocnemis tropix (Australian tarantula spider).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Araneae; Mygalomorphae; Theraphosidae; Coremiocnemis.
OX   NCBI_TaxID=1904443;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 49-87, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=27793656; DOI=10.1016/j.toxicon.2016.10.013;
RA   Ikonomopoulou M.P., Smith J.J., Herzig V., Pineda S.S.,
RA   Dziemborowicz S., Er S.Y., Durek T., Gilchrist J., Alewood P.F.,
RA   Nicholson G.M., Bosmans F., King G.F.;
RT   "Isolation of two insecticidal toxins from venom of the Australian
RT   theraphosid spider Coremiocnemis tropix.";
RL   Toxicon 123:62-70(2016).
CC   -!- FUNCTION: This toxin causes paralysis and death to sheep
CC       blowflies. It does not target insect sodium channels.
CC       {ECO:0000250|UniProtKB:P0DL77, ECO:0000250|UniProtKB:P0DL81}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27793656}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:27793656}.
CC   -!- PTM: Contains 3 disulfide bonds. Two different connectivities are
CC       observed in similar proteins (C1-C3, C2-C5, C4-C6 or C1-C4, C2-C5,
CC       C3-C6). {ECO:0000305|PubMed:27793656}.
CC   -!- MASS SPECTROMETRY: Mass=4239.675; Method=MALDI; Range=45-82;
CC       Note=Monoisotopic mass.; Evidence={ECO:0000269|PubMed:27793656};
CC   -!- MISCELLANEOUS: No effect of the synthetic peptide are observed on
CC       voltage-gated sodium channels from the American cockroach
CC       Periplanata americana or the German cockroach Blattella germanica.
CC       {ECO:0000250|UniProtKB:P0DL77}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 12 (Hwtx-2) family. 03
CC       (juruin) subfamily. {ECO:0000305}.
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DR   SMR; P0DL78; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR012625; Toxin_20.
DR   Pfam; PF08089; Toxin_20; 1.
DR   PROSITE; PS60022; HWTX_2; 1.
PE   1: Evidence at protein level;
KW   Calcium channel impairing toxin; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Neurotoxin; Secreted;
KW   Signal; Toxin; Voltage-gated calcium channel impairing toxin.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   PROPEP       24     44       {ECO:0000269|PubMed:27793656}.
FT                                /FTId=PRO_0000442237.
FT   CHAIN        45     82       U1-theraphotoxin-Ct1b.
FT                                {ECO:0000269|PubMed:27793656}.
FT                                /FTId=PRO_0000442238.
SQ   SEQUENCE   82 AA;  9137 MW;  140E1A2CB9C8764F CRC64;
     MRTFTLIAIL TCALLVIYHA AEAEELEAKD VIESKALATL DEERFECSLS CDIKKNGKPC
     KGSGEKKCSG GWRCKMNFCL KF
//